Syntheses and crystal structure of a (2,6-diisopropyldinaphtho[2,1-d:1′,2′-f][1,3]dithiepin-4-yl)(phenyl)methanol atropisomer

The molecular and crystal structure is reported for the major diastereoisomer formed in a sterically hindered reaction of a substituted dinaphthodithiepine. The structure lends support to a reaction mechanism and transition state postulated to explain the experimentally determined preferential formation of this diastereoisomer over the minor component.


Chemical context
In the continuing pursuit of stereoselective synthetic methodology, steric considerations play an important role. Indeed, defined by steric limitations are the atropisomers of biaryl compounds formed as a result of restricted rotation about the connecting single bonds (Cen et al., 2022;Wencel-Delord et al., 2015;Cheng et al., 2021). For 1,1 0 -binaphthalenes, functionalization of the 2,2 0 positions with a dithiapine ring helps to lock the atropisomers against inversion and facilitates studies of diastereoselective reactions. An example of such reactions is the attack of the sulfur-stabilized dinaphthodithiepine carbanion on a prochiral electrophile Delogu et al., 1991;Beare et al., 2023). Reaction of the organolithium of dinaphtho[2,1d:1 0 ,2 0 -f][1,3]dithiepine, and various substituted derivatives with benzaldehyde (and other prochiral ketones) proceeded in high chemical yield and gave readily separable alcohol products, allowing the diastereomeric excess to be quantified (Painter, 1995;Beare, 1999). The results suggested the structure of the organolithium species is significant in determining the stereoselectivity, and that in all cases the same diastereoisomer (aS,R/aR,S) forms the major product (Delogu et al., 1991;Beare et al., 2023).
This work reports the synthesis and single-crystal X-ray structure of the major diastereoisomer of (2,6-diisopropyldinaphtho[2,1-d:1 0 ,2 0 -f][1,3]dithiepin-4-yl)(phenyl)methanol, C 34 H 32 OS 2 , 1, formed from the reaction of the carbanion of 2,6-diisopropyldinaphtho[2,1-d:1 0 ,2 0 -f][1,3]dithiepine (2) with benzaldehyde. The stereochemistry is confirmed as aS,R/aR,S. We postulate that the preference for this geometry is a transition state that minimizes steric interactions between the incoming ketone and proximal 3,3 0 binaphthalene substituents, isopropyl groups in the case of 1. Intramolecular O-HÁ Á ÁS hydrogen bonds (described below) also provide a model for predicted lithium-sulfur interactions that stabilize the transition state and lithio salt, prior to the quenching of the reaction. A reaction mechanism showing carbanion (3) attack of the R atropisomer at the Re face of benzaldehyde to form the major aR,S diastereoisomer is illustrated in Fig. 1.

Structural commentary
In 1 (Fig. 2), a 1,1 0 -linked binaphthalene is functionalized at the 2,2 0 positions with disulfaneylmethane. The seven-membered ring formed locks the binaphthalene ring system into R and S atropisomers of pseudo-C 2 symmetry. The individual naphthalene ring systems are predictably flat, with r.m.s. deviations from the ten-atom mean plane of 0.017 and 0.026 Å for C101-C110 and C201-C210, respectively. The C102-C101-C201-C202 torsion angle is À68.8 (4) , and the dihedral angle between the naphthalene ring mean planes is 70.4 (1) . The structure is extended with a chiral benzyl alcohol substituent on the methylene bridge carbon atom, giving aS,R and aR,S enantiomer pairs. The alcohol group of the molecule is positioned such that an intramolecular hydrogen bond forms to one of the bridge sulfur atoms (Table 1, Fig. 3). The same feature has been observed in the closely related structure with Cambridge Structural Database refcode NEWVOE . Completing the structural description are isopropyl residues on the 3-and 3 0 -positions of the binaphthalene unit that are arranged so as to minimize steric interaction with the thioacetal core, but The molecular structure of 1 with displacement ellipsoids drawn at the 50% probability level. Carbon atoms C107-C109 follow the logical progression but their labels are omitted for clarity.

Figure 1
Proposed reaction and transition state for the carbanion attack of the R atropisomer at the Re face of benzaldehyde. Table 1 Hydrogen-bond and C-HÁ Á Á geometry (Å , ).

Synthesis and crystallization
The synthesis of 1 is a multistep process (Fig. 6), but can be summarized as follows: preparation of the isopropyl-substi-tuted binaphthalene diol (6); conversion to the dithiol (9) exploiting the Newman-Kwart thermorearrangement of the The intramolecular O-HÁ Á ÁS hydrogen bond and short C-HÁ Á ÁS contacts of 1.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.